Alterations in gastrointestinal motility assessed by high-resolution antroduodenal manometry in patients with severe disorders of gut-brain interaction.

INTRODUCTION: Data are limited regarding gastrointestinal motility disturbance in disorders of gut-brain interaction (DGBI). This study aimed to characterize antroduodenal motor alterations in patients using high-resolution antroduodenal manometry (HR-ADM). METHODS: HR-ADM was performed in patients with severe DGBI and compared with healthy volunteers (HV). HR-ADM used a commercially available probe composed of 36 electronic sensors spaced 1 cm apart and positioned across the pylorus. Antral and duodenal motor high-resolution profiles were analyzed, based on the frequency, amplitude, and contractile integral/sensor (CI/s) calculated for each phase of the migrating motor complex (MMC). RESULTS: Eighteen HV and 64 patients were investigated, 10 with irritable bowel syndrome (IBS), 24 with functional dyspepsia (FD), 15 with overlap IBS-FD, and 15 with other DGBI. Compared with HV, patients had a lower frequency of phase II duodenal contractions (27 per hour vs 51; p=0.002) and a lower duodenal phase II contraction amplitude (70 mmHg vs 100; p=0.01) resulting in a lower CI/s of phase II (833 mmHg.cm.s vs 1901; p<0.001) in the duodenum. In addition, the frequency of phase II propagated antroduodenal contractions was lower (5 per hour vs 11; p<0.001) in patients, as compared to HV. Interestingly, the antral CI/s of phase III was decreased in FD patients, but not in IBS patients. CONCLUSION: Patients with severe DGBI display alterations in antral and intestinal motility assessed using commercially available HR-ADM. Whether these alterations may explain symptom profiles in such patients remains to be confirmed. (NCT04918329 and NCT01519180).

Physiological characterization of gastric emptying using high-resolution antropyloroduodenal manometry.

Delayed gastric emptying (GE) has been associated with antral and pyloric dysmotility. We aimed to characterize differences in the antral, duodenal, and pyloric motility profiles associated with delayed GE, using high-resolution antropyloroduodenal manometry (HR-ADM). Patients referred for HR-ADM for dyspeptic symptoms performed a concurrent GE breath test (NCT01519180 and NCT04918329). HR-ADM involved 36 sensors 1 cm apart, placed across the pylorus. Interdigestive and postprandial periods were identified. Antral, pyloric, and duodenal motor profiles were analyzed recording the frequency, amplitude, and propagative nature of contractions for each period. Plots of patients with normal and delayed GE were compared. Sixty patients underwent both HR-ADM and GE tests. Twenty-five and 35 patients had delayed and normal GE, respectively. Antral and duodenal motor profiles were not different between the two groups during the interdigestive period. During the postprandial period, a lower frequency of antral contractions was associated with delayed GE (2.22 vs. 1.39 contractions/min; P = 0.002), but no difference in mean contraction amplitude was observed. The pyloric region was identified in all the patients and pylorospasms, defined as 3 min of repeated isolated pyloric contractions, were more frequent in patients with delayed GE (32.0% vs. 5.7%; P = 0.02) during the postprandial period. No difference in duodenal contraction profiles was observed. Manometric profile alterations were observed in 72% of the patients with delayed GE, with 56% having a low frequency of antral contractions. Using HR-ADM, patients with delayed GE displayed different postprandial antropyloric motility as compared with patients with normal GE.NEW & NOTEWORTHY High-resolution antropyloroduodenal manometry (HR-ADM) allows precise characterization of antral, pyloric, and duodenal motility, although its association with gastric emptying (GE) has been poorly investigated. Concurrent HR-ADM with GE measurement showed a lower frequency of antral postprandial contractions and an increased frequency of postprandial pylorospasms in patients with delayed GE. HR-ADM could, therefore, be useful in the future to better select patients for treatments targeting the pylorus.

Transanal irrigation is a better choice for bowel dysfunction in adults with Spina bifida: A randomised controlled trial.

AIM: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients. METHODS: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis. RESULTS: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10. CONCLUSIONS: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.

Evaluation of the efficacy of sacral neuromodulation in the treatment of voiding dysfunction after endometriosis surgery.

Pelvic surgery for endometriosis is associated with a risk of bladder and digestive sequelae. Sacral neuromodulation (SNM) has been shown to be effective in the treatment of overactive bladder (OAB) and voiding dysfunction (VD). This study aimed to evaluate the efficacy of sacral neuromodulation (SNM) in treating voiding dysfunction (VD) following endometriosis surgery. A retrospective analysis was conducted on data from women who underwent SNM testing for persistent VD after endometriosis surgery. The study included 21 patients from a French tertiary referral center. Patient characteristics, lower urinary tract symptoms, urodynamic findings, SNM procedures, and outcomes were assessed. The primary outcome was the success of SNM treatment for VD. After a median follow-up of 55 months, 60% of patients achieved successful outcomes, with significant improvements of VD and quality of life. Moreover, more than half of patients who required clean intermittent self-catheterization (CISC) before SNM were able to wean off CISC. Complications such as infections and paraesthesia were observed, but overall, SNM was found to be effective and well tolerated. Age and the interval between endometriosis surgery and SNM testing were associated with treatment success. This study adds to the limited existing literature on SNM for VD after endometriosis surgery and suggests that SNM can be a valuable therapeutic option for these patients. Further research is needed to identify predictive factors and mechanisms underlying the effectiveness of SNM in this context. MRI-compatible and rechargeable devices, has improved the feasibility of SNM for these patients. In conclusion, SNM offers promise as a treatment option for persistent VD after endometriosis surgery, warranting further investigation. LEVEL OF EVIDENCE: 4.

Ten-year Evaluation of a Large Retrospective Cohort Treated by Sacral Nerve Modulation for Fecal Incontinence: Results of a French Multicenter Study.

OBJECTIVE: The aim of this study was to assess the effectiveness of sacral nerve modulation (SNM) in a large cohort of patients implanted for at least 10 years, quantify adverse event rates, and identify predictive factors of long-term success. SUMMARY BACKGROUND DATA: Few studies have evaluated the long-term success of SNM. METHODS: Data collected prospectively from patients implanted for fecal incontinence (FI) in 7 French centers between January 1998 and December 2008 were retrospectively analyzed. Patient FI severity scores were assessed before and 10 years after implantation. The main evaluation criterion was the success of SNM defined by the continuation of the treatment without additional therapies. The secondary evaluation criteria were the rate of device revisions and explantations. Preoperative predictors of success at 10 years were sought. RESULTS: Of the 360 patients (27 males, mean age: 59 ± 12 years) implanted for FI, 162 (45%) had a favorable outcome 10 years post-implantation, 115 (31.9%) failed, and 83 (23.1%) were lost to follow-up. The favorable outcome derived from the time-to-event Kaplan-Meier curve at 10 years was 0.64 (95% CI 0.58-0.69). FI severity scores were significantly better 10 years post-implantation compared to preimplantation (7.4 ± 4.3 vs 14.0 ± 3.2; P < 0.0001). During the 10-year follow-up, 233 patients (64.7%) had a surgical revision and 94 (26.1%) were explanted. A history of surgery for FI and sex (male) were associated with an increased risk of an unfavorable outcome. CONCLUSIONS: Long-term efficacy was maintained in approximately half of the FI patients treated by SNM at least 10 years post-implantation.

Relationship between anal functional lumen imaging probe (EndoFLIP®) results and the clinical presentation of faecal incontinence.

AIM: Faecal incontinence (FI) subtypes (urge, passive, mixed) are linked to the physiopathological mechanism of FI. Previous studies have failed to demonstrate a consistent relationship between FI subtype and anal sphincter dysfunction. Our aim was to evaluate the relationship between anal sphincter function, assessed using the new EndoFLIP® technology, and FI subtype. METHOD: Patients referred for FI were prospectively enrolled between October 2015 and May 2021 in a registry, and data were retrospectively examined. Each patient underwent a clinical assessment as well as three-dimensional high-resolution or water-perfused anorectal manometry, anal EndoFLIP®, and anorectal electrophysiological and endoanal ultrasound tests. The results of the investigations were compared across FI subtypes. RESULTS: The cohort included 133 patients, 54 (41%) of whom met the criteria for urge FI, 40 (30%) for passive FI and 39 (29%) for mixed FI. The resting anal distensibility index (DI) at 50 ml of distension was significantly lower in patients with urge FI than in patients with passive FI (p = 0.04). At rest, a DI at 50 ml of distension ≥7.3 mm2  mmHg-1 and a DI at 40 ml of distension <1.3 mm2  mmHg-1 were associated with the passive and urge FI subtypes, respectively, with poor discriminatory power (an accuracy of 0.49 compared with 0.33 for random assignment). There were no differences in anorectal manometry, endoanal ultrasound or electrophysiological test results among the urge, passive and mixed FI subgroups (all p > 0.05). CONCLUSION: The anal sphincter DI using the EndoFLIP® system displayed poor predictive performance in distinguishing among FI subtypes.

Is sacral nerve modulation reprogramming effective after permanent implantation for faecal incontinence?

AIM: Sacral nerve modulation (SNM) is recommended as a first-line surgical therapy for patients with faecal incontinence (FI). During patient follow-up, it is recommended that stimulation settings be reprogrammed to optimize patient outcomes. The aim of the present study was to evaluate the efficacy of stimulator reprogramming in patients with an implanted SNM device to treat FI. METHOD: The data from patients who received a permanent SNM implant in a single centre from January 2008 to December 2019 were retrospectively analysed. Symptoms that occurred after implantation, the stimulator settings of the SNM device and changes made at each follow-up visit were noted. The efficacy of reprogramming was determined by assessing patient satisfaction. RESULTS: Of the 117 patients (male/female 4/113; mean age 59.5 ± 11.8 years) with a SNM implant for FI, 84 (72%) had at least one symptom requiring reprogramming of the stimulator, most often during the first year after implantation (p = 0.05). The most frequently reported symptoms were loss of efficacy (68.5%; p = 1 × 10-3 ) and pain (20.5%; p = 1 × 10-3 ). Reprogramming was effective 53% of the time when treating loss of efficacy and 76% of the time when treating pain. When the stimulation parameters were reprogrammed at least four consecutive times to correct a symptom, the reprogramming was less effective in treating the symptom (p = 0.02). CONCLUSION: Regular follow-up of patients with SNM device implants associated with reprogramming of stimulation parameters to improve the treatment of reported symptoms would optimize the efficacy of SNM.

Sacral neuromodulation with the InterStim™ system for faecal incontinence: results from a prospective French multicentre observational study.

AIM: The aim of this work was to evaluate the effectiveness, patient satisfaction and quality of life (QoL) and the safety of sacral neuromodulation (SNM) with the InterStimTM system for the treatment of faecal incontinence (FI) and establish whether results published predominantly by expert sites are generalisable. METHOD: This is a prospective, multicentre, observational study that invited all French sites treating FI with the InterStim™ system to enrol subjects indicated for an SNM therapy evaluation. Data were collected at three follow-up visits within 1 and 15 months. Therapeutic effectiveness was evaluated by the reduction in leakages per week and improvements over time in the ability to defer defaecation and QoL (as measured with the Faecal Incontinence Quality of Life score). Safety was assessed through reported adverse events. RESULTS: A total of 221 subjects with a mean age of 62.1 years were tested (184 women) and 178 received a permanent implant. For all implanted subjects with diary data at baseline and follow-up, a reduction in leakage of more than 50% was observed in 80%, 76% and 83% at 1-3, 4-8 and 9-15 months, respectively. The mean number of leakage episodes and urgency improved significantly compared with the baseline (p < 0.0001). Subjects showed improvements in QoL and time to defer defaecation and were generally satisfied with their therapy. The main device-related adverse event was the requirement to undertake reprogramming (in 52% of subjects with actions following an event). The rates of infection (in 6% of subjects) and surgical revision (in 10% of subjects) were in agreement with literature reports. CONCLUSION: This study confirms the clinical effectiveness, safety and positive effect of SNM on QoL as well as high patient satisfaction for the treatment of FI in real-life.

Assessment of anal sphincter distensibility following the STARR procedure: a pilot study.

Aim: The STARR (Stapled Trans-Anal Rectal Resection) procedure consists of a surgical correction of symptomatic rectocele refractory to medical treatment, involving anal dilatation. The aim of the study was to determine the impact of the STARR procedure on anal distensibility using EndoFLIP® device.Methods: All female patients with a minimal rectocele of 3 cm and with symptoms of obstructed defecation syndrome (ODS) refractory to medical treatment were included prospectively. Patients with previous anal incontinence were not included. Wexner, ODS and Kess scores were recorded. Endoanal ultrasounds and EndoFLIP® measurements were performed pre-surgery and 3 months following the STARR procedure. The distensibility index (DI) at 40 mL of inflation at rest was the primary study endpoint.Results: Seven patients (median age: 52.5, range: 44-62) were included between 2014 and 2017. The DI after surgery was the same as the pre-surgery DI. No patient developed symptoms of faecal incontinence or urge to defecate in the three months following the STARR procedure. All patients reported an improvement in their ODS and Kess scores three months after the STARR procedure. No anal sphincter defects were detected by endoanal ultrasound.Conclusion: Anal dilatation did not appear to alter anal distensibility in patients with a normal anal function before the STARR procedure.

Pyloric distensibility measurement predicts symptomatic response to intrapyloric botulinum toxin injection.

BACKGROUND AND AIMS: Recent studies have reported that pyloric distensibility was altered in 30% to 50% of patients with gastroparesis, and this was correlated with gastric emptying and symptom severity. The aim of this study was to assess whether pyloric distensibility measurement was predictive of symptomatic response after intrapyloric botulinum toxin (BT) injection. METHODS: Pyloric distensibility was measured using the EndoFLIP system (Crospon, Galway, Ireland) before intrapyloric BT injection. Altered pyloric distensibility was defined as distensibility below 10 mm2/mm Hg. Total symptomatic score (TSS), dyspeptic symptoms, Gastrointestinal Quality of Life Index (GIQLI), and gastric emptying were investigated prospectively before and 3 months after BT injection. RESULTS: Nineteen of 35 patients had altered pyloric distensibility. In those patients, TSS decreased at 3 months from 13.5 to 10.5 (P < .01), whereas it remained unchanged in patients with normal pyloric distensibility (P = .7). Gastric fullness (from 3.5 to 2.5; P = .03) and bloating (from 3.0 to 2.0; P = .01) were the only symptoms that improved in patients with altered pyloric distensibility, whereas none of them was improved in patients with normal pyloric distensibility. GIQLI score increased from 59.5 to 76.5 in patients with altered pyloric distensibility (P = .02), whereas there was no statistical difference (P = .43) in patients with normal pyloric distensibility. In patients with altered pyloric distensibility, gastric emptying half time was 223 minutes before and 190 minutes 3 months after injection (P = .02), whereas it remained unchanged in patients with normal pyloric distensibility (P = .6). CONCLUSIONS: Pyloric distensibility measurement before intrapyloric BT injection predicted symptomatic and quality of life response 3 months after injection in patients with gastroparesis.

Does Bilateral Deep Brain Stimulation of the Subthalamic Nucleus Modify Ano-Rectal Motility in Parkinson's Disease? Results of a Randomized Cross-Over Study.

BACKGROUND: Ano-rectal motility impairment is often observed during Parkinson's disease (PD), generating symptoms as constipation and/or incontinence with impaired quality of life. Subthalamic nuclei (STN) deep brain stimulation (DBS) improves motor symptoms of PD, but its effects on anorectal motility are unknown. This study aimed to assess the effects of STN-DBS on the anorectal motility in PD patients, in a randomized cross-over study. METHODS: Sixteen PD patients with bilateral STN-DBS for at least 6 months were included. The anal resting pressure, duration and maximal amplitude of squeeze effort, recto-anal inhibitory reflex, maximal tolerable rectal volume, and anal pressure during defecation effort were measured and compared after STN-DBS was switched OFF and then ON for 2 hours, or vice-versa, in a randomized order. KEY RESULTS: STN-DBS increased maximal amplitude of anal squeezing pressure (OFF: 85.7 ± 14.5 vs ON: 108.4 ± 21.0 cmH2 O; P = 0.02), with no significant difference in the duration (P = 0.10). No other significant difference was found between stimulation conditions (OFF vs ON) for anal resting pressure (OFF: 72.5 ± 8.6 cmH2 O vs ON: 71.7 ± 9.0 cmH2 O; P = 0.24), recto-anal inhibitory reflex, maximal tolerable rectal volume (OFF: 231 ± 24 mL vs ON: 241 ± 26 mL; P = 0.68), or anal pressure during defecation effort with a similar rate of ano-rectal dyssynergia (7/16 and 8/16 with and without STN-DBS, respectively). No order effect (ON-OFF vs OFF-ON) was observed. CONCLUSION AND INFERENCES: STN-DBS increased anal squeezing pressure, but did not modify anorectal dyssynergia in PD patients, This study demonstrated the involvement of STN in the voluntary control of anorectal motility in PD patients.

Development of a Remote-Controlled Implantable Rat Sacral Nerve Stimulation System.

OBJECTIVES: Sacral nerve stimulation (SNS) is a surgical treatment of urinary and fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS are still poorly known. This may be related to the use of acute stimulation models. Up to date, no rodent model of chronic SNS implants has been developed. Therefore, the aim of this study was to create a fully implantable and remotely controllable stimulating device to establish an animal model of chronic SNS. MATERIALS AND METHODS: The stimulating device consisted of an implantable pulse generator linked to a platinum electrode. The communication with the device was made through an inductive link which allowed to adjust the stimulation parameters; that is, to turn the device on and off or check the battery status remotely. Rats underwent two surgical procedures. In the first procedure, we achieved chronic sacral stimulation but the implanted electrode was not fixated. In the second procedure, the electrode was fixated in the sacral foramen using dental resin. In both cases, the correct positioning of the electrode was evaluated by computed tomography (CT) imaging and the presence of tail tremor in response to high intensity stimulation. We only tested the function of implanted electrode with fixation using micturition frequency assessment following bipolar or unipolar SNS for three days after recovery. RESULTS: CT imaging showed that implantation of the electrode required fixation as we found that the second surgical procedure yielded a more precise placement of the implanted electrode. The correct placement of implanted electrode observed with imaging was always correlated with a successful tail tremor response in rats, therefore we pursued our next experiments with the second surgical procedure and only assessed the tail tremor response. We found that both bipolar and unipolar SNS reduced micturition frequency. CONCLUSION: This stimulating device provides an efficient method to perform chronic SNS studies in rats.

Is Sacral Nerve Modulation a Good Option for Fecal Incontinence in Men?

OBJECTIVE: The objective was to assess the efficacy and the safety of sacral nerve modulation (SNM) in men with fecal incontinence (FI) compared with those of SNM in women. METHOD: Prospectively collected data from patients from seven tertiary colorectal units who underwent an implant procedure between January 2010 and December 2015 were reviewed retrospectively. Outcomes and surgical revision and definitive explantation rates were compared between men and women. RESULTS: A total of 469 patients (60 men [12.8%]; mean age = 61.4 ± 12.0 years) were included in the study, 352 (78.1%) (31 men [8.8%]) of whom received a permanent implant. The ratio of implanted/tested men was significantly lower than the ratio of implanted/tested women (p = 0.0004). After a mean follow-up of 3.4 ± 1.9 years, the cumulative successful treatment rates tended to be less favorable in men than in women (p = 0.0514): 88.6% (75.6-95.1), 75.9% (60.9-86.4), 63.9% (48.0-77.3), and 43.9% (26.7-62.7) at one, two, three, and five years, respectively, in men; 92.0% (89.1-94.2), 84.2% (80.3-87.4), 76.8% (72.3-80.7), and 63.6% (57.5-69.3) at one, two, three, and five years, respectively, in women. The revision rate for infection and the definitive explantation rate for infection were higher in men than in women (p = 0.0001 and p = 0.0024, respectively). CONCLUSION: Both short- and long-term success rates of SNM for FI were lower in men than in women. The revision and definitive explantation for long-term infection rates were significantly higher in men.

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS).

OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. RESULTS: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

Botulinum toxin: an endoscopic approach for treating fecal incontinence.

BACKGROUND AND STUDY AIMS: Fecal incontinence is a common, distressing condition with limited therapeutic options. Botulinum toxin A (BTX-A) injections have been proposed as a treatment for patients with fecal incontinence. This study aimed to determine the short-term clinical outcomes of BTX-A injections in patients with fecal incontinence of varying etiology. PATIENTS AND METHODS: Twenty-six patients with fecal incontinence were enrolled, 17 with their native rectum and 9 with a neo-reservoir following a proctectomy for rectal cancer. BTX-A was endoscopically injected into the rectum/reservoir. Scores for severity (CCS) and quality of life (FIQL) were recorded at baseline and at the 3-month follow-up visit. RESULTS: The CCS was significantly lower after 3 months (median 15, range 4 - 20 vs. 8, range 1 - 19; P = 0.001). The quality of life improved in three of the four FIQL domains. The improvement was maintained in 11 of 12 patients who received more than one injection because of recurrent symptoms. There was no significant predictive factor for the success of BTX-A injections. CONCLUSION: This preliminary study demonstrated that rectal/reservoir injections are an effective short-term treatment for fecal incontinence.

Predictive factors for successful sacral nerve stimulation in the treatment of fecal incontinence: lessons from a comprehensive treatment assessment.

BACKGROUND: Sacral nerve stimulation has a place in the treatment algorithm for fecal incontinence, but the predictive factors of its midterm and long-term success are unknown. OBJECTIVE: The purpose of this study was to investigate the effect of a 3-year sacral nerve stimulation treatment of fecal continence and to identify specific predictive factors from the pretreatment and per-treatment assessments for the midterm success of sacral nerve stimulation. DESIGN: A cohort analysis of consecutive patients treated with sacral nerve stimulation for fecal incontinence over a period of 3 years was performed. SETTINGS: This study was conducted at an academic colorectal unit in a tertiary care center. PATIENTS: Sixty patients were available for the assessment of 3-year outcomes. MAIN OUTCOME MEASURES: Clinical outcome (including Cleveland Clinic score) and anorectal physiological data were collected prospectively before and after treatment. RESULTS: At the 3-year follow-up, 33 of the 60 implanted patients had an improved outcome as defined by a ≥30% improvement in the Cleveland Clinic score from baseline (37.1% on intention to treat and 55.0% per protocol), whereas 22 had an unsuccessful outcome as defined by a <30% improvement in the Cleveland Clinic score from baseline (24.7% on intention to treat and 36.7% per protocol), of whom 7 had their device explanted or switched off permanently before the 3-year assessment, and 3 were lost at follow-up. At 3 years, we failed to identify any factors that could predict the 3-year clinical outcome of sacral nerve stimulation based on preimplantation and postimplantation assessments. LIMITATIONS: This study involved a relatively small number of patients. There was a lack of consistency in the tool used to evaluate the efficacy of the test and permanent stimulations. CONCLUSIONS: Based on per-protocol assessments, 55% of the patients had improved outcomes at the 3-year follow-up. No predictor was identified by the pretreatment and posttreatment assessments (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A133).

Fecal Incontinence Subtype Assessment (FI-SA): Validation of a new tool to distinguish among subtypes of fecal incontinence.

PURPOSE: Three subtypes of fecal incontinence (FI) are described in the literature: urge, mixed and passive FI, but the relevance of this classification remains unknown. To our knowledge, no questionnaire has been validated in a general population of patients with FI to classify patients between the different subtypes of FI. The aim of the present study was to validate the Fecal Incontinence Subtype Assessment (FI-SA) questionnaire in a general population of patients with FI. METHODS: All consecutive patients referred to our unit for physiological investigations of anorectal function in case of FI were included. A feasibility study was done to assess the acceptability, understanding, and the reproducibility of the FI-SA questionnaire. Its performance to correctly classify patients between subtypes of FI was evaluated in both a feasibility study and in a validation study, using clinical interview as gold standard. RESULTS: The FI-SA questionnaire was found to be well accepted and easily understood by patients. Moreover, it was filled rapidly by patients, with a good reproducibility with an intra-class correlation coefficient of 0.97 and 0.87 for questions 1 and 2. Lastly, the accuracy of the FI-SA questionnaire to predict subtypes of FI was 93.3 % in the feasibility study (n = 30) and 81.1 % in the validation study (n = 100), in comparison with clinical interview as gold standard. CONCLUSION: The FI-SA questionnaire could be used in the future to help standardize the methodology used among studies to evaluate the classification of patients in different subtypes of FI and ultimately to guide therapeutics.

Intrarectal injections of botulinum toxin versus placebo for the treatment of urge faecal incontinence in adults (FI-Toxin): a double-blind, multicentre, randomised, controlled phase 3 study.

BACKGROUND: Non-randomised studies assessing intrarectal botulinum toxin type A (BoNTA) injections for faecal incontinence are promising. We aimed to evaluate the efficacy of BoNTA for the treatment of faecal incontinence in a randomised study. METHODS: In this randomised, double-blind, placebo-controlled study, we included adult patients who had at least one urgency or faecal incontinence episode per week for at least 3 months and who had experienced a failure of conservative or surgical treatment from eight French specialist hospital units with the skills to manage patients with faecal incontinence. Patients were randomly assigned (1:1) by a central web form to receive intrarectal submucosal injections of either 200 units of BoNTA (Botox; Allergan, Irvine, CA, USA; BoNTA group) or an equivalent volume of saline (placebo group), stratified by Cleveland Clinic Severity scores (CCS score; ≥12 or <12). Patients, investigators, study site staff, and sponsor personnel were masked to treatment allocation up to the 6-month visit. The primary endpoint was the number of episodes of faecal incontinence and urgency per day assessed using 21-day patient bowel diaries 3 months after the treatment. The primary analysis was performed using a modified intention-to-treat (mITT) approach (ie, in all the randomised patients who had received a treatment) with adjustment for baseline faecal incontinence and urgency episodes. After the final data collection at 6 months after injections, patients were unmasked and offered the BoNTA treatment if they were in the placebo group (rescue therapy) without masking, with an additional 6 months of safety follow-up. This trial is registered with ClinicalTrials.gov, number NCT02414425. FINDINGS: Between Nov 25, 2015, and Nov 25, 2020, we randomly assigned 200 patients to receive either BoNTA (n=100) or placebo (n=100) injections. Due to withdrawals before the injections, 96 patients were included in the BoNTA group and 95 patients were included in the placebo group (mITT analysis). The mean number of faecal incontinence and urgency episodes per day in the BoNTA group decreased from 1·9 (SD 2·2) at baseline to 0·8 (1·8) at 3 months after the injections, and from 1·4 (1·1) to 1·0 (1·0) in the placebo group, with a baseline-adjusted mean group difference at 3 months estimated at -0·51 (95% CI -0·80 to -0·21, p=0·0008). No serious treatment-related adverse events were reported in the trial. The most frequently reported non-serious adverse event (treatment related or not) following the BoNTA or placebo injections was constipation (reported in 68 [40%] of 169 patients who received the BoNTA injections and 38 [40%] of 95 patients who received placebo injections). INTERPRETATION: BoNTA injections are an efficacious treatment for urge faecal incontinence. Further research will define the optimum selection criteria, dose, site of injection, re-injection frequency, and long-term results. FUNDING: General Direction of Healthcare (French Ministry of Health).

Delayed gastric emptying determined using the 13C-octanoic acid breath test in patients with systemic sclerosis.

OBJECTIVE: To determine the prevalence of delayed gastric emptying using the 13C-octanoic acid breath test in unselected patients with systemic sclerosis (SSc), to evaluate whether findings of the 13C-octanoic acid breath test are associated with clinical digestive manifestations, gastric mucosal abnormalities detected by gastroscopy, motor activity dysfunction detected by antroduodenal manometry, and esophageal motor impairment and extradigestive manifestations of SSc, and to develop a risk prediction score of gastric emptying in SSc. METHODS: Consecutive patients with SSc (n=57) underwent the 13C-octanoic acid breath test. All of the patients with SSc completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. RESULTS: The prevalence of delayed gastric emptying was 47.4% in patients with SSc. A marked correlation was observed between a GSS of digestive symptoms≥5 and the presence of delayed gastric emptying (P<0.00001). The sensitivity of a GSS≥5 for predicting delayed gastric emptying was as high as 0.93, while the specificity was 0.73. Moreover, a GSS≥5, mucosal gastric abnormalities, severe esophageal motor impairment, and interstitial lung disease were factors that were independently associated with the presence of delayed gastric emptying, and these variables were used to create a risk prediction score. The area under the receiver operating characteristic curve for the risk prediction score was 0.90; the sensitivity of this score for the prediction of delayed gastric emptying was 0.93, while the specificity was 0.77. CONCLUSION: The results indicate that delayed gastric emptying occurs often in patients with SSc. Interestingly, using risk models with routine clinical characteristics, a simple risk prediction score can be calculated, allowing prediction of the occurrence of delayed gastric emptying in patients with SSc.

Multiple sclerosis and bowel symptoms: Frequency and barriers to their management.

BACKGROUND: The frequency of bowel symptoms (BSs) is still a matter for debate in multiple sclerosis (MS) patients. However, BSs have been shown to cause significant distress. Our study aimed to (i) investigate the frequency of BSs, particularly those that are not managed, (ii) identify potential predictors for help-seeking care for patients with BSs, and (iii) evaluate the ability of the Neurogenic Bowel Dysfunction (NBD) score to screen for BSs. METHOD: Three hundred sixty-nine MS patients completed a cross-sectional demographic and clinical survey of MS and BSs and their management. RESULTS: BSs were reported by 47.7% of MS patients. Eighty-eight percent of MS patients had a very minor-minor Neurogenic Bowel Disorder (NBD) score and 12% had a moderate-severe NBD score. Forty-one percent of patients did not report their BS to a healthcare provider, mainly because they preferred not to talk about the problem. BS duration was the only significant predictor of help-seeking for BS management. Female sex, visual impairment, a digestive history, and longer MS duration were good predictors of BSs. Patients with BSs (86%) were correctly identified with an NBD score >2. CONCLUSION: BSs are under-detected in MS populations. This is partially related to non-declaration by patients. Targeting BSs using the NBD score is a good way to increase reporting.